The broad objectives of this project is the elucidation of the etiology and pathogenesis of sarcoidosis so that a soundly based program of prevention and therapy can be established for this widespread systemic disorder. The hub of the project is the systematic effort to purify, isolate and characterize by currently available chemical, physical, isotopic and immunologic techniques, the active component(s) in human sarcoidal tissues which are responsible for eliciting specifically a positive intracutaneous Kveim reaction in subjects with sarcoidosis. Other segments of this project involve the establishment of an appropriate animal model to define more precisely the immunologic determinants of granuloma formation which may prove applicable to other granulomatous disorders, such as Crohn's disease, leprosy, beryllium disease etc. An effective animal model could serve to evaluate therapeutic agents which might prevent granuloma formation or cause resolution of granulomas, subsequently to be applied, if feasible, to the treatment of human sarcoidosis and other granulomatous disorders. In search for an in-vitro Kveim test, further observations of peripheral lymphocytes and, more recently, of monocytes from patients with sarcoidosis, are being pursued. Until a replacement for the intracutaneous Kveim test is devised, a supply of standardized and continuously monitored Kveim suspensions will be maintained at the Sarcoidosis Laboratory at the Mount Sinai School of Medicine, where it has served since 1960 as an international reference standard against which newly submitted Kveim suspensions processed in other laboratories has been calibrated. A bank of 14 human sarcoidal spleens is maintained for future research and clinical application.